pediatric lupus nephritis
Conditions
Interventions
Patient Group:During the screening period, eligible subjects who met the inclusion criteria were administered the study drug at baseline (Day 0), 7, 14, 21, 28 days, and then weekly for a total treatm
Sponsors
Children’s Hospital of Fudan University
Eligibility
Sex/Gender
All
Age
5 Years to 17 Years
Inclusion criteria
Inclusion criteria: The following inclusion criteria must be met for subjects to be enrolled in this trial: 1. Male or female children aged 5 to 17 years. 2. Children diagnosed with Systemic Lupus Erythematosus (SLE) based on the 2012 SLICC or 2019 EULAR/ACR classification criteria. 3. Patients with active, biopsy-proven Class III or IV proliferative lupus nephritis [except III(C), IV-S(C), and IV-G(C) types], with or without Class V, or isolated Class V membranous lupus nephritis according to the 2003 ISN/RPS criteria. The biopsy should not have been performed earlier than 6 months before the screening visit or during the screening period. Local biopsy reports will be used to confirm subject eligibility. 4. Positive antinuclear antibodies (ANA) and/or positive serum anti-dsDNA antibodies at screening. 5. Record of active renal disease at screening with a Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score =8 and initiation of standard treatment: Standard treatment includes glucocorticoids, antimalarials, and immunosuppressants (1. cyclophosphamide, 2. mycophenolate mofetil or other oral forms of mycophenolate, or 3. tacrolimus). Active renal disease is defined by the following criteria: ?Urinary protein/creatinine ratio =1.0 and - Active urinary sediment [meeting at least one of the following criteria (excluding menstrual period and urinary or genital tract infection)]: a. >5 red blood cells (RBCs)/high-power field (HPF) or higher than the laboratory reference range. b. >5 white blood cells (WBCs)/HPF or higher than the laboratory reference range. c. Presence of cellular casts (RBC or WBC). - Subjects without active urinary sediment can be eligible if they meet at least one of the following criteria: a. A confirmatory renal biopsy performed within the last 3 months before screening or during the screening period, with results meeting the inclusion criteria. b. Urinary protein =30-50 mg/kg/day (or urinary protein/creatinine ratio =2.0). 6. Subjects with the above-defined active renal disease at screening will receive the recommended doses of the standard treatment as follows, which may be adjusted due to tolerability issues: a. Glucocorticoids: Prednisone at a dose of 1.0-2.0 mg/kg/day, with a maximum daily dose of 60 mg/day (or equivalent). Methylprednisolone pulse therapy at a dose of 15-30 mg/kg/infusion (recommended not to exceed 750 mg/infusion) for 1-2 courses may be chosen based on the child's condition and risk-benefit assessment. b. Cyclophosphamide (CYC): Monthly intravenous infusion of 500 mg/m2, with a maximum of 1 g per month, for a total of 6 infusions (maximum cumulative dose of 6 g). c. Mycophenolate mofetil (MMF): Oral administration at a dose of 20-40 mg/kg/day, divided into two doses (12-hour intervals), with a maximum oral dose of 1.5-2 g/day. Drug concentration monitoring and dose adjustment are recommended (Note: MMF-AUC target concentration is 40-60 mg*h/L). d. Tacrolimus (FK506): Oral administration at a dose of 0.05-0.1 mg/kg/day, divided into two doses, with a maximum oral dose of 3 mg/day. Dose adjustment based on drug trough concentration monitoring is recommended (Note: The target concentration for FK506 trough level is 5-10 ng/µL). e. Previous treatment with intravenous immunoglobulin (IVIG) or blood purification during the induction period is allowed. 7. Female subjects who are not pregnant or lactating are eligible for enrollment. 8. The child's legal guardian or the child themselves must have the ability to u
Exclusion criteria
Exclusion criteria: Participants will be excluded from the trial if they meet any of the following exclusion criteria: 1.Known allergy or contraindication to any drugs planned for use in the study (e.g., CYC, MMF, FK506, glucocorticoids), or any components of the aforementioned drugs. 2.History of allergic reactions to human or murine proteins or monoclonal antibodies. 3.Prior treatment with Telitacicept at any time. 4.Receipt of B-cell-targeted therapies within 180 days prior to baseline (Day 0), including Belimumab, Rituximab, other anti-CD20 agents, anti-CD22 agents (Epratuzumab), anti-CD52 agents (Alemtuzumab), TACI-Fc, etc. 5.Receipt of interleukin-6 (IL-6) targeted therapy within 364 days prior to baseline (Day 0), e.g., Tocilizumab (Actemra). 6.Receipt of any of the following treatments within 90 days prior to baseline (Day 0): anti-tumor necrosis factor (anti-TNF) therapy (e.g., Adalimumab, Etanercept, Infliximab, Golimumab, Certolizumab Pegol), interleukin-1 receptor antagonist (Anakinra), JAK inhibitors, etc. 7.Receipt of live vaccines within 30 days prior to baseline (Day 0). 8.Receipt of any dose of intravenous immunoglobulin (IVIG) within 30 days prior to baseline (Day 0). 9.Occurrence of severe active central nervous system lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accidents, encephalitis, or central nervous system vasculitis) requiring therapeutic intervention within 90 days prior to baseline (Day 0). 10.Receipt of blood purification within 30 days prior to baseline (Day 0) or planned need for blood purification during the study due to the disease condition. 11.Estimated glomerular filtration rate (eGFR) <60 mL/minute/1.73 m2 at screening visit (calculated using the modified Schwartz equation: eGFR [ml/(min·1.73 m2)] = k × height (cm)/Scr (µmol/L), where k = 36.5). 12.History or planned of transplantation of solid organ (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/bone marrow. 13.Clinical evidence of major non-SLE-related, significant unstable or poorly controlled acute or chronic diseases (e.g., cardiovascular, pulmonary, hematological, gastrointestinal, hepatic, renal, neurological, malignant, or infectious diseases) that the principal investigator considers could confound study results or pose excessive risk to the participant. 14.Planned surgical procedure or any disease or laboratory abnormality that the principal investigators consider unsuitable for participation in the trial (e.g., cardiovascular or pulmonary disease, difficult establishment of venous access). 15.History of malignancy within the past 5 years, excluding adequately treated non-melanoma skin cancer (basal cell carcinoma or squamous cell carcinoma) or carcinoma in situ of the cervix. 16.Acute or chronic infections requiring treatment, including: ?Chronic infections under suppressive therapy (e.g., tuberculosis, Pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria). ?Hospitalization for treatment of severe infection (e.g., lobar pneumonia, sepsis, central nervous system infection) within 30 days prior to baseline (Day 0). 17.Past or screening positive for HIV antibody. 18.Hepatitis B: Based on results of HBsAg, anti-HBc, and anti-HBs, serological evidence of hepatitis B (HB) infection is present, as follows: ?Patients with positive HBsAg are excluded. ?Patients with negative HBsAg but positive anti-HBc antibodies, regardless of their anti-HBs antibody status, require HBV DNA testi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish a population pharmacokinetic (PopPK) model for Telitacicept in chidlren with lupus nephritis (LN); | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety of Telitacicept in pediatric LN;Primary efficacy renal response (PERR) and no renal response at Week 12 and Week 24;SLE Responder Index-4 (SRI-4) response at Week 12 and Week 24;Proportion of patients with a =4-point reduction in SLEDAI score at Week 12 and Week 24;Steroid dose and proportion of patients on =10 mg/day of steroids at Week 24; | — |
Countries
China
Contacts
Public ContactLi Sun
Children’s Hospital of Fudan University
Outcome results
None listed